Journal article
Elucidating the motif for cpg oligonucleotide binding to the dendritic cell receptor dec-205 leads to improved adjuvants for liver-resident memory
J Li, F Panetta, M O'Keeffe, IML Rojas, KJ Radford, JG Zhang, D Fernandez-Ruiz, GM Davey, BS Gully, KM Tullett, J Rossjohn, R Berry, CN Lee, MH Lahoud, WR Heath, I Caminschi
Journal of Immunology | AMER ASSOC IMMUNOLOGISTS | Published : 2021
Abstract
DEC-205 is a cell-surface receptor that transports bound ligands into the endocytic pathway for degradation or release within lysosomal endosomes. This receptor has been reported to bind a number of ligands, including keratin, and some classes of CpG oligodeoxynucleotides (ODN). In this study, we explore in detail the requirements for binding ODNs, revealing that DEC-205 efficiently binds single-stranded, phosphorothioated ODN of ≥14 bases, with preference for the DNA base thymidine, but with no requirement for a CpG motif. DEC-205 fails to bind double-stranded phosphodiester ODN, and thus does not bind the natural type of DNA found in mammals. The ODN binding preferences of DEC-205 result i..
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Awarded by Mater Foundation
Funding Acknowledgements
This work was supported by the National Health and Medical Research Council of Australia (NHMRC) Grant APP1060522 and Australian Research Council (ARC) Grant CEI140100011 (to J.R) . W.R.H. and M.O.K. are supported by NHMRC fellowships. K.J.R. is supported by the Mater Foundation. M.O.K., K.J.R., I.C., W.R.H., J-G.Z., D. F-R., and M.H.L. are supported by project grants from the NHMRC of Australia. J.R., W.R.H., and J-G.Z. are supported by NHMRC Program grants. J. R. is supported by an ARC Laureate Fellowship. J.L., F.P., I.M.L.R, J-G.Z, D. F-R., G.M.D., B.S.G., K.M.T., and C-N. L. performed experiments; M.O.K., K.J.R., J.R., R.B., M.H.L. provided expertise and conceptual advice for different aspects of the study; W.R.H. and I.C. conceived and designed the study and wrote the manuscript.